Transcriptional response of Candida albicans biofilms following exposure to 2-amino-nonyl-6-methoxyltetralin muriate  

作　　者：Rong-mei LIANG Yong-bing CAO You-jun ZHOU Yi XU Ping-hui GAO Bao-di DAI Feng YANG Hui TANG Yuan-ying JIANG 

机构地区：[1]Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China [2]Department of Pharmacy, General Hospital of Chengdu Military Command Region, Chengdu 610083, China [3]Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China [4]Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China

出　　处：《Acta Pharmacologica Sinica》2010年第5期616-628,共13页中国药理学报（英文版）

基　　金：Acknowledgements We thank Dr William A FONZI for kindly offering the isolate C albicans SC5314 in this study. This work was supported by the National Natural Science Foundation of China （30825041, 30500628, and 30630071）, National Basic Research Project （2005CB523105）, National High Technology Research and Development Program 863 of China （2008AA02Z302）.

摘　　要：Aim： To identify changes in the gene expression profile of Candida albicans （C albicans） biofilms following exposed to 2-amino-nonyl-6- methoxyl-tetralin muriate（lOb） and clarify the mechanism of lOb against C albicans biofilms. Methods： Anti-biofilm activity of lOb was assessed by tetrazolium （XTT） reduction assay and the action mechanism against biofllms was investigated by cDNA microarray analysis and real-time RT-PCR assay. Results： Ten differentially expressed genes were directly linked to biofilm formation and filamentous or hyphal growth （eg, NRG1, ECE1 and CSA1）. Decreased gene expression was involved in glycolysis （eg, HXK2 and PFK1） and antioxidant defense （eg, SOD5）, while increased gene expression was associated with enzymes that specifically hydrolyzed 13-1,3 glucan （XOG1）, and with lipid, fatty acid and sterol metabolism （eg, SLD1, ERG6 and ERG2）. Functional analysis indicated that addition of anti-oxidant ascorbic acid reduced inhibitory efficiency of lOb on mature biofilm. Conclusion： Inhibition of lOb on biofilm formation possibly depends on impairing the ability of C albicans to change its morphology via altering the expression of biofilm formation genes. Mitochondrial aerobic respiration shift and endogenous ROS augmentation might be a major contribution to reduce mature biofilm metabolic activity. The data may be useful for the development of new strategies to reduce the incidence of device-associated infections.Aim： To identify changes in the gene expression profile of Candida albicans （C albicans） biofilms following exposed to 2-amino-nonyl-6- methoxyl-tetralin muriate（lOb） and clarify the mechanism of lOb against C albicans biofilms. Methods： Anti-biofilm activity of lOb was assessed by tetrazolium （XTT） reduction assay and the action mechanism against biofllms was investigated by cDNA microarray analysis and real-time RT-PCR assay. Results： Ten differentially expressed genes were directly linked to biofilm formation and filamentous or hyphal growth （eg, NRG1, ECE1 and CSA1）. Decreased gene expression was involved in glycolysis （eg, HXK2 and PFK1） and antioxidant defense （eg, SOD5）, while increased gene expression was associated with enzymes that specifically hydrolyzed 13-1,3 glucan （XOG1）, and with lipid, fatty acid and sterol metabolism （eg, SLD1, ERG6 and ERG2）. Functional analysis indicated that addition of anti-oxidant ascorbic acid reduced inhibitory efficiency of lOb on mature biofilm. Conclusion： Inhibition of lOb on biofilm formation possibly depends on impairing the ability of C albicans to change its morphology via altering the expression of biofilm formation genes. Mitochondrial aerobic respiration shift and endogenous ROS augmentation might be a major contribution to reduce mature biofilm metabolic activity. The data may be useful for the development of new strategies to reduce the incidence of device-associated infections.

关 键 词：2-amino-nonyl-6-methoxyl-tetralin muriate anti-biofilm activity action mechanism microarray analysis Candida albicans 

分 类 号：R[医药卫生]